One of the diseases with the highest incidence but which lacks effective treatment is obesity. It is a debilitating condition which reduces quality of life and substantially increases the risk of other diseases.
In the USA 25% of the adult population is now considered to be clinically obese. It has been estimated that $45 billion of US healthcare costs, or 8% per annum of total healthcare spend, is a direct result of obesity. In Europe the problem is increasing. It has been predicted that without new approaches over 20% of the UK population will be clinically obese by 2005. The fact that obesity is a metabolic disease is being increasingly recognized by the medical profession and the health authorities. There is, however, a shortage of effective and safe drugs which can be used in conjunction with diet and exercise for the long-term management of obesity.
It is an object of the present invention to provide such drugs and also to provide means to identify and develop further such drugs.
Preproglucagon is a 160 amino acid polypeptide which is cleaved in a tissue specific manner by prohormone convertase-1 and -2 giving rise to a number of products with a variety of functions in both the central nervous system (CNS) and peripheral tissues. In the intestine and in the CNS, the major post-translational products of preproglucagon cleavage are glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), glicentin and oxyntomodulin (OXM), as shown in Figure A. While GLP-1 and GLP-2 have been shown to inhibit food intake, no such role has been demonstrated in humans for the distinct peptide OXM. The importance of OXM as a biologically active peptide in humans has not been demonstrated.